Manufacturing permanently-sterile injection liquids



Patented Sept. 16,- 1930 UNITED STATES PATENT OFFICE ERICE SCHULZE, OF HANOVER, GERMANY, ASSIGNOR '10 KARL SOHRADER, DIE HANOVER, GERMANY MANUFACTURING PERMANENTLY-STERILE INJECTION LIQUIDS No Drawing. Application filed July 23, 1925, Serial No. 45,717, and in Germany July 23, 1924,

This invention has reference to the manufacture of injection or other liquids for dental, medicinal and other purposes, and particularly for local anaesthesia by means .of

which practically permanent injection liquids proof against the action of bacteria, as well as against other infecting agents, such as schizomycetes, fungus growth, putrefac'tion and the like are obtained, and

without the objectionable, irritating and other injurious action heretofore experienced with a great many of the solutionsre ferred to. The sterilization of injection liq uids, particularly for subcutaneous use or 5 local anaesthesia was heretofore elfected mostly by mechanical or physical means or by the addition of such substances, such as phenol, cresol, thymol and the like whichproduced serious irritating action and injury to the tissue and were also open to other objectionable action; nor was it possible to arrive at a reliable permanent sterilization by the means referred to. Thus for instance,

the small bulbs or ampoules, and the like kinds of injection liquid and sterilized by mechanical or physical means, while by themselves sterile under certain conditions, have been known to soon lose their absolute freedom from germs after being opened either by infection from the tool employed in opening them or, by the entrance of air containing bacteria, or by the introduction of an injector which is not absolutely free from germs. While with the judicious and most careful employment of special kinds of injection needles, draining needles, tubings or canules, extensions and the like, it has been possible to prevent any most serious contamination of the solution, yet, a perfeet and permanent sterilization of the solution could never be depended upon, and as a matter of fact the presence of micro-organisms with the use of the processes heretofore employed has been ascertained and proved in many cases.

Now, my invention has reference to a method by means of which it is possible to produce an absolutely reliable permanent so sterility of injection liquids without intercomposition, and

now in use and filled with the most varying fering with their keeping qualities and their particularly in the case of injection liqui s for local anaesthesia, such as for example, novocain solutions that is to say solutions of para-amino-benzoyl-diethyl-amino-ethanol-hydrochloride of the usual composition, by making an addition of small amounts of certain quinine-alkaloids, to which in certain cases carbolic acid or phenol or benzoic acid or a mixture of the same or homologues may be added. Of the alkaloids referred to it hasv been ascertained that particularly the alkyl-compounds of the hydro-quinine with from 5 to 8 atoms of carbon in the lateral chain of the quinoline-nucleus are highly efiicient for the purpose in question, such as for instance the eucupine or iso-amyl-hydrocupreine, and the vuzine or iso-octyl-hydrocupreine, and furthermore those compounds obtained by the splitting up of the quinoline-nucleus by prolonged heating with acetic acid, and containing the carbonyl group C=O and designated as quina toxines in view of their specific poisonous action upon micro-organisms, and of these particularly the vuzinotoxine has been found to be particularly suitable. These compounds are also scientifically designated as hydrocupreicines (compare Henry, PlantAlkaloids 1924, age 171), the quinatoxine product obtained rom vuzin being scientifically termed iso-octylhydrocupreicine, these bodies being moreover derivatives of quinicine. It has been ascertained from the specific poisonous action of these compounds against micro-organisms that these compounds may be employed in such minute quantities for the urpose of producing by themselves abso ute permanent sterilization in injection solutions that any liability of irritation of the tissue, and of excitation of the patient consequent thereon are excluded.

In further pursuance of my invention the sterility and activity of these quininealkaloids, particularly in the case of protection from putrefaction germs, schizomycetes and the like, and from the action of ferments may be. further increased b the treatment with very small quantities o carbolic acid or to the phenols or with benzoic acid or with both'of them combined. 1

While the employment of carbolic acid as a sterilizing addition to injection solutions is by itself known, such addition was made heretofore in such concentrations that it was relied upon to be able to act. as a bactericide itself, that is to say in concentrations of 2% and above. In such concentrations, however, the carbolic acid produces very serious injuries to the tissue and irritation, inasmuch as a twonerves. Now, it is a very important element of the formation of'mould. It

, to which has beenadded one drop of a 10% of my invention that the carbolic acid is employed at a considerably lower concentration, in which concentration the carbolic acid is not any more able to kill the bacteria, while it 'will yet produce a preventing or retarding action uponthe decomposition of the organisms which have been killed by vuzinoalcoholic solution of vuz inotoxin-hydrochlorid, is already sufiicient to obtain a perfectly and permanently sterile injection solution of excellent keeping qualities, and not subject to quantities that the benzoic acid is neither .suflicient as a bactericide nor destructive to decomposition or to the formation of mould, while perfectly agreeing with and not m jurious. to the'animal tissues.

The carb'ohc acid or phenols may be re placed or be used in conjunction with benzoic acid, 'the solution and addition ofbenzoic' acid being likewise employed in such small the tissue. It is, for instance, suflicient to add benzoic acid to a solution of novocain to which has been previously added one drop amounting to about a minim or say about 0.07 cc. of a 10% solution of vuzi-no-toxin hy- I 'drochloridin alcohol, 0.1 to 0.2% of benzoic",

acid being added in order-toobtain a perfectly and permanently sterile and keeping injection solution which is not subject to decial attention to 'the presence of putrefactlon bacteria, it is in most cases sufiicient to mere-- 1y add a small amount of the toxine to the solution to be protected, and. in this case I compositlon, putrefaction or formation of mould, and which is suitable and perfectly agreeing even withithe'most delicate and sensible tissues", and persons.

rcent solution is already'i njurious bers and cel-lules of the animal hydrochlorid? It is obvious that the concentration may be varied in accordance with particular requirements. It sho d also be pointed out in this connection that the invention may find expression in many l other embodiments to better adapt the same to varying conditions of application, and that changes and modifications .are possible within the spirit and scope. of

my invention, as particularly set forth in the ap nded claims.

tainedboth for dental as .well'as for general medicinal and surgical uses.

Iclaim:--' I I 1. An injection liquid containing. an novocaine and a small quantity of a solution of vuzi'no-quinaealkalold.

2. An jection solution of high sterility,

containing very small quantities averaging up to about 2 to 3-hundredths of a. gram of hydro-cupreicine's in 100 cc.

3. An injection solution of high sterility,

1 containing very small quantities averagmg up to about '2 to 3-hundredths of a gram of iso-hydro-octyl-cupreicine in 100 1 I 4. An injection liquid, containing very small quantities averaging up to "about 2 to 3-hundredths of a gram of hydrocupreicinealkaloids in 100 cc. and such small quantities of oxy-benzols of acid reaction, as will exclude irritative and destructive action on animal tissues.

5-. All injection liquid of, high sterility, 1

containingon an average up fito about 2 to 3- hundredths of a gram. of the hydrochlorid of hydroc'upreicines.

6. An injection liquid of high sterility, containing on an average u to about 2 to 3- hundredths of a gram 0 iso-octyl-hydrocu reicine in one hundred part of liquid.

An injection liquid of high sterility, containing on an average up to about 2 to 3- hundredths of a gram of iso-octyl-hydrocupreicine-hydrochlorid and tenths of a gram of oxy-benzols-of acid reaction to one hundred parts of liquid.

8. An injectionliquid containing novocaine and a small quantity of up to 2 to 3- hundredths of a gram to hundred parts of this means injection solutions are obliquid on an average of an alcoholic solution of iso-octyl-hydrocupreicinehydrochlorid, q ERICH'SCHULZE.

Where there is no neoesslty of paying .spe- I 7 may, for instance, proceed as .foll'oWsz- A 2 to 4% solution'of novocain is treated with about one drop amounting'to about a or'say about 0.07 cc.v of a ten- 8 percent alcohohc solution of .vuz in'o-toxin 

